최준호
2019-11-26T04:09:23Z
2019-11-26T04:09:23Z
2017-06
NATURE COMMUNICATIONS, v. 8, Article no. 15730
2041-1723
https://www.nature.com/articles/ncomms15730
https://repository.hanyang.ac.kr/handle/20.500.11754/114508
Misfolded polypeptides are rapidly cleared from cells via the ubiquitin-proteasome system (UPS). However, when the UPS is impaired, misfolded polypeptides form small cytoplasmic aggregates, which are sequestered into an aggresome and ultimately degraded by aggrephagy. Despite the relevance of the aggresome to neurodegenerative proteinopathies, the molecular mechanisms underlying aggresome formation remain unclear. Here we show that the CTIF-eEF1A1-DCTN1 (CED) complex functions in the surveillance of either pre-existing or newly synthesized polypeptides by linking two molecular events: selective recognition and aggresomal targeting of misfolded polypeptides. These events are accompanied by CTIF sequestration into the aggresome, preventing the additional synthesis of misfolded polypeptides from mRNAs bound by nuclear cap-binding complex. These events render cells more resistant to apoptosis induced by proteotoxic stresses. Collectively, our data provide compelling evidence for a previously unappreciated protein surveillance pathway and a regulatory gene expression network for coping with misfolded polypeptides.
We thank Ron R. Kopito for providing plasmid expressing CFTR-DF508, Elizabeth S. Sztul for plasmid expressing GFP-250, Tso-Pang Yao for plasmid expressing FLAG-HDAC6, Michael Y. Sherman for plasmids expressing GFP-SYN1 and mRFP-Ub, Eui-Ju Choi for plasmid expressing FLAG-SOD1, Berndt Muller for the antibody against human SLBP, Sung Hoon Back for MEF-eIF2 alpha (A/A) cells and Sung Key Jang for plasmid expressing GST. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP; NRF-2015R1A3A2033665).
en_US
NATURE PUBLISHING GROUP
MESSENGER-RNA DECAY
PROTEIN-QUALITY CONTROL
ELONGATION-FACTOR 1A
CAP-BINDING COMPLEX
CBP80/20-DEPENDENT TRANSLATION
NEURODEGENERATIVE DISEASES
CYTOPLASMIC DYNEIN
AGGREGATION
HISTONE
DEGRADATION
Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex
Article
10.1038/ncomms15730
NATURE COMMUNICATIONS
Park, Joori
Park, Yeonkyoung
Ryu, Incheol
Choi, Mi-Hyun
Lee, Hyo Jin
Oh, Nara
Kim, Kyutae
Kim, Kyoung Mi
Choe, Junho
Lee, Cheolju
2017003407
S
COLLEGE OF NATURAL SCIENCES[S]
DEPARTMENT OF LIFE SCIENCE
jcho2711
E-3410-2019
http://orcid.org/0000-0002-2365-3755